Whole-Genome Sequencing for Investigating a Health Care-Associated Outbreak of Carbapenem-Resistant

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2021 Feb 12

PMID 33573077

Citations 14

Authors

Sang Mee Hwang

Hee Won Cho

Tae Yeul Kim

Jeong Su Park

Jongtak Jung

Kyoung-Ho Song

Hyunju Lee

Eu Suk Kim

Hong Bin Kim

Kyoung Un Park

Affiliations

Soon will be listed here.

Abstract

Carbapenem-resistant (CRAB) outbreaks in hospital settings challenge the treatment of patients and infection control. Understanding the relatedness of clinical isolates is important in distinguishing outbreak isolates from sporadic cases. This study investigated 11 CRAB isolates from a hospital outbreak by whole-genome sequencing (WGS), utilizing various bioinformatics tools for outbreak analysis. The results of multilocus sequence typing (MLST), single nucleotide polymorphism (SNP) analysis, and phylogenetic tree analysis by WGS through web-based tools were compared, and repetitive element polymerase chain reaction (rep-PCR) typing was performed. Through the WGS of 11 isolates, three clonal lineages were identified from the outbreak. The coexistence of and with additional aminoglycoside-inactivating enzymes, predicted to confer multidrug resistance, was identified in all isolates. The MLST Oxford scheme identified three types (ST191, ST369, and ST451), and, through whole-genome MLST and whole-genome SNP analyses, different clones were found to exist within the MLST types. wgSNP showed the highest discriminatory power with the lowest similarities among the isolates. Using the various bioinformatics tools for WGS, CRAB outbreak analysis was applicable and identified three discrete clusters differentiating the separate epidemiologic relationships among the isolates.

Citing Articles

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References

Kim M, Jeong H, Sim Y, Lee S, Yong D, Ryu C . Using comparative genomics to understand molecular features of carbapenem-resistant Acinetobacter baumannii from South Korea causing invasive infections and their clinical implications. PLoS One. 2020; 15(2):e0229416. PMC: 7034955. DOI: 10.1371/journal.pone.0229416. View

Fitzpatrick M, Ozer E, Hauser A . Utility of Whole-Genome Sequencing in Characterizing Acinetobacter Epidemiology and Analyzing Hospital Outbreaks. J Clin Microbiol. 2015; 54(3):593-612. PMC: 4767972. DOI: 10.1128/JCM.01818-15. View

Brettin T, Davis J, Disz T, Edwards R, Gerdes S, Olsen G . RASTtk: a modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes. Sci Rep. 2015; 5:8365. PMC: 4322359. DOI: 10.1038/srep08365. View

Rossen J, Friedrich A, Moran-Gilad J . Practical issues in implementing whole-genome-sequencing in routine diagnostic microbiology. Clin Microbiol Infect. 2017; 24(4):355-360. DOI: 10.1016/j.cmi.2017.11.001. View

Castillo-Ramirez S, Grana-Miraglia L . Inaccurate Multilocus Sequence Typing of Acinetobacter baumannii. Emerg Infect Dis. 2018; 25(1):186-187. PMC: 6302598. DOI: 10.3201/eid2501.180374. View

Ellington M, Ekelund O, Aarestrup F, Canton R, Doumith M, Giske C . The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria: report from the EUCAST Subcommittee. Clin Microbiol Infect. 2016; 23(1):2-22. DOI: 10.1016/j.cmi.2016.11.012. View

Grana-Miraglia L, Lozano L, Velazquez C, Volkow-Fernandez P, Perez-Oseguera A, Cevallos M . Rapid Gene Turnover as a Significant Source of Genetic Variation in a Recently Seeded Population of a Healthcare-Associated Pathogen. Front Microbiol. 2017; 8:1817. PMC: 5611417. DOI: 10.3389/fmicb.2017.01817. View

Weiner L, Webb A, Limbago B, Dudeck M, Patel J, Kallen A . Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011-2014. Infect Control Hosp Epidemiol. 2016; 37(11):1288-1301. PMC: 6857725. DOI: 10.1017/ice.2016.174. View

Harris S, Cartwright E, Torok M, Holden M, Brown N, Ogilvy-Stuart A . Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study. Lancet Infect Dis. 2012; 13(2):130-6. PMC: 3556525. DOI: 10.1016/S1473-3099(12)70268-2. View

10.

Li W, Raoult D, Fournier P . Bacterial strain typing in the genomic era. FEMS Microbiol Rev. 2009; 33(5):892-916. DOI: 10.1111/j.1574-6976.2009.00182.x. View

11.

Lewis T, Loman N, Bingle L, Jumaa P, Weinstock G, Mortiboy D . High-throughput whole-genome sequencing to dissect the epidemiology of Acinetobacter baumannii isolates from a hospital outbreak. J Hosp Infect. 2010; 75(1):37-41. DOI: 10.1016/j.jhin.2010.01.012. View

12.

Boolchandani M, DSouza A, Dantas G . Sequencing-based methods and resources to study antimicrobial resistance. Nat Rev Genet. 2019; 20(6):356-370. PMC: 6525649. DOI: 10.1038/s41576-019-0108-4. View

13.

Dymond A, Davies H, Mealing S, Pollit V, Coll F, Brown N . Genomic Surveillance of Methicillin-resistant Staphylococcus aureus: A Mathematical Early Modeling Study of Cost-effectiveness. Clin Infect Dis. 2019; 70(8):1613-1619. PMC: 7145999. DOI: 10.1093/cid/ciz480. View

14.

Liu F, Zhu Y, Yi Y, Lu N, Zhu B, Hu Y . Comparative genomic analysis of Acinetobacter baumannii clinical isolates reveals extensive genomic variation and diverse antibiotic resistance determinants. BMC Genomics. 2014; 15:1163. PMC: 4367897. DOI: 10.1186/1471-2164-15-1163. View

15.

Snitkin E, Zelazny A, Montero C, Stock F, Mijares L, Murray P . Genome-wide recombination drives diversification of epidemic strains of Acinetobacter baumannii. Proc Natl Acad Sci U S A. 2011; 108(33):13758-63. PMC: 3158218. DOI: 10.1073/pnas.1104404108. View

16.

Clausen P, Aarestrup F, Lund O . Rapid and precise alignment of raw reads against redundant databases with KMA. BMC Bioinformatics. 2018; 19(1):307. PMC: 6116485. DOI: 10.1186/s12859-018-2336-6. View

17.

Wattam A, Davis J, Assaf R, Boisvert S, Brettin T, Bun C . Improvements to PATRIC, the all-bacterial Bioinformatics Database and Analysis Resource Center. Nucleic Acids Res. 2016; 45(D1):D535-D542. PMC: 5210524. DOI: 10.1093/nar/gkw1017. View

18.

Koser C, Ellington M, Cartwright E, Gillespie S, Brown N, Farrington M . Routine use of microbial whole genome sequencing in diagnostic and public health microbiology. PLoS Pathog. 2012; 8(8):e1002824. PMC: 3410874. DOI: 10.1371/journal.ppat.1002824. View

19.

MacCannell D . Bacterial strain typing. Clin Lab Med. 2013; 33(3):629-50. DOI: 10.1016/j.cll.2013.03.005. View

20.

Lee S, Oh M, Yun S, Choi C, Park E, Song H . Genomic characterization of extensively drug-resistant Acinetobacter baumannii strain, KAB03 belonging to ST451 from Korea. Infect Genet Evol. 2018; 65:150-158. DOI: 10.1016/j.meegid.2018.07.030. View